Genetic conservation of the immunophilin-binding domains of human calcineurin A1 and A2

Iain J. Brogan, Vera Pravica, Ian V. Hutchinson

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Calcineurin a calmodulin-dependent phosphatase plays a critical role in calcium-dependent activation of T-lymphocytes and is the major target for the inhibitory actions of the immunosuppressive drugs Tacrolimus (FK506) and Cyclosporin A (CsA). Calcineurin is a dimeric protein consisting of distinct A (catalytic) and B (regulatory) subunits. In humans two separate genes, CNA1 and CNA2, encode the calcineurin A (CNA) subunit. The region of CNA that interacts with Calcineurin B, calmodulin, and immunosuppressive drugs bound to their receptors - the immunophilins - has been identified to amino acids 281-414 (Greengard P, Allen PB, Nairin AC. Beyond the dopamine receptor: the DARPP-32/protein phosphatase-1 cascade. Neuron 1999;23:435). Our working hypothesis was that the differences in patient response to calcineurin inhibitors could be a consequence of inherited variations within their CNA genes. Single-strand conformational polymorphism (SSCP) analysis of cDNAs derived from the coding region for amino acids 281-414 of CNA1 and CNA2 in 32 healthy Caucasians did not detect polymorphic variations within these genes. These results suggest that this region is highly conserved and cannot account for individual variation in response of patients to FK506 and CsA treatment. (C) 2000 Elsevier Science B.V. All rights reserved.
    Original languageEnglish
    Pages (from-to)139-141
    Number of pages2
    JournalTransplant immunology
    Volume8
    Issue number2
    Publication statusPublished - 2000

    Keywords

    • Calcineurin
    • Immunophilin
    • Immunosuppressive
    • Polymorphism

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